Co‐occurrence of astrocytoma and astroblastoma: Case report and literature review

A 41‐year‐old man presented to us with left arm and leg weakness and mild word finding difficulties. His preoperative magnetic resonance imaging (MRI) demonstrated abnormal T1 and T2 signal changes in the right temporal lobe and basal ganglia, indicative of possible glioma. An awake craniotomy for right temporal lobectomy was performed and the tumor was resected. Full pathologic workup later revealed the patient had two distinct tumors occurring simultaneously, anaplastic astrocytoma and astroblastoma. We review the literature regarding the treatment of anaplastic astrocytoma and astroblastoma and discuss their co‐occurrence.     

VEGFA From Early Osteoblast Lineage Cells (Osterix+) Is Required in Mice for Fracture Healing

Bone formation via intramembranous and endochondral ossification is necessary for successful healing after a wide range of bone injuries. The pleiotropic cytokine, vascular endothelial growth factor A (VEGFA) has been shown, via nonspecific pharmacologic inhibition, to be indispensable for angiogenesis and ossification following bone fracture and cortical defect repair. However, the importance of VEGFA expression by different cell types during bone healing is not well understood. We sought to determine the role of VEGFA from different osteoblast cell subsets following clinically relevant models of bone fracture and cortical defect. Ubiquitin C (UBC), Osterix (Osx), or Dentin matrix protein 1 (Dmp1) Cre-ERT2 mice (male and female) containing floxed VEGFA alleles (VEGFA^fl/fl) were either given a femur full fracture, ulna stress fracture, or tibia cortical defect at 12 weeks of age. All mice received tamoxifen continuously starting 2 weeks before bone injury and throughout healing. UBC Cre-ERT2 VEGFA^fl/fl (UBC cKO) mice, which were used to mimic nonspecific inhibition, had minimal bone formation and impaired angiogenesis across all bone injury models. UBC cKO mice also exhibited impaired periosteal cell proliferation during full fracture, but not stress fracture repair. Osx Cre-ERT2 VEGFA^fl/fl (Osx cKO) mice, but not Dmp1 Cre-ERT2 VEGFA^fl/fl (Dmp1 cKO) mice, showed impaired periosteal bone formation and angiogenesis in models of full fracture and stress fracture. Neither Osx cKO nor Dmp1 cKO mice demonstrated significant impairments in intramedullary bone formation and angiogenesis following cortical defect. These data suggest that VEGFA from early osteolineage cells (Osx+), but not mature osteoblasts/osteocytes (Dmp1+), is critical at the time of bone injury for rapid periosteal angiogenesis and woven bone formation during fracture repair. Whereas VEGFA from another cell source, not from the osteoblast cell lineage, is necessary at the time of injury for maximum cortical defect intramedullary angiogenesis and osteogenesis. © 2019 American Society for Bone and Mineral Research.     

Microduplication of Xp11.23p11.3 with effects on cognition,behavior, and craniofacial development

El‐Hattab AW, Bournat J, Eng PA, Wu JBS, Walker BA, Stankiewicz P, Cheung SW, Brown CW. Microduplication of Xp11.23p11.3 with effects on cognition, behavior, and craniofacial development. We report an ～1.3 Mb tandem duplication at Xp11.23p11.3 in an 11‐year‐old boy with pleasant personality, hyperactivity, learning and visual‐spatial difficulties, relative microcephaly, long face, stellate iris pattern, and periorbital fullness. This clinical presentation is milder and distinct from that of patients with partially overlapping Xp11.22p11.23 duplications which have been described in males and females with intellectual disability, language delay, autistic behaviors, and seizures. The duplicated region harbors three known X‐linked mental retardation genes: FTSJ1, ZNF81, and SYN1. Quantitative polymerase chain reaction from whole blood total RNA showed increased expression of three genes located in the duplicated region: EBP, WDR13, and ZNF81. Thus, over‐expression of genes in the interval may contribute to the observed phenotype. Many of the features seen in this patient are present in individuals with Williams‐Beuren syndrome (WBS). Interestingly, the SYN1 gene within the duplicated interval, as well as the STX1A gene, within the WBS critical region, co‐localize to presynaptic active zones, and play important roles in neurotransmitter release.     

One-year Treatment of Morpholino Antisense Oligomer Improves Skeletal and Cardiac Muscle Functions in Dystrophic mdx Mice

Antisense therapy has been successful to skip targeted dystrophin exon with correction of frameshift and nonsense mutations of Duchenne muscular dystrophy (DMD). Systemic production of truncated but functional dystrophin proteins has been achieved in animal models. Furthermore, phase I/II clinical trials in United Kingdom and the Netherlands have demonstrated dystrophin induction by local and systemic administrations of antisense oligomers. However, long-term efficacy and potential toxicity remain to be determined. The present study examined 1-year systemic effect of phosphorodiamidate morpholino oligomers (PMO) treatment targeting mutated dystrophin exon 23 in mdx mice. PMO induced dystrophin expression dose-dependently and significantly improved skeletal muscle pathology and function with reduced creatine kinase (CK) levels by a regimen of 60 mg/kg biweekly administration. This regimen induced <2% dystrophin expression in the heart, but improved cardiac functions demonstrated by hemodynamics analysis. The results suggest that low levels of dystrophin induction may be able to provide detectable benefit to cardiac muscle with limited myopathy. Body weight, serum enzyme tests, and histology analysis showed no sign of toxicity in the mice treated with up to 1.5 g/kg PMO for 6 months. These results indicate that PMO could be used safely as effective drugs for long-term systemic treatment of DMD.     

Impaired reading comprehension in schizophrenia: evidence for underlying phonological processing deficits

The present study examined reading ability in high functioning people with schizophrenia. To this end, 16 people with schizophrenia who were living in the community and 12 matched controls completed tests of passage reading (comprehension, accuracy, and rate), word recognition, and phonological processing (phonological awareness, phonological memory and rapid naming) and ratings of reading self-concept and practices. Performance of the participants with schizophrenia was impaired relative to control participants on reading comprehension and rapid naming and relative to the population norms on phonological awareness, and rapid naming. In addition, self-rating data revealed that participants with schizophrenia had poorer perceptions of their reading ability and engaged in reading activities less frequently than their control counterparts. Consistent with earlier research, significant correlations were found between phonological awareness and reading comprehension. These findings expand on previous research in the area to suggest that community-based individuals with schizophrenia experience problems with reading comprehension that may have a phonological basis.     

Age- and gender-specific risk of death after first hospitalization for heart failure

Background  

Hospitalization for heart failure (HF) is associated with high-in-hospital and short- and long-term post discharge mortality. Age and gender are important predictors of mortality in hospitalized HF patients. However, studies assessing short- and long-term risk of death stratified by age and gender are scarce.     

Intranasal delivery of DNA encoding antigens of Mycobacterium tuberculosis by non-pathogenic invasive Escherichia coli

Naturally invasive bacteria have been successfully used for mucosal delivery of DNA vaccines against bacterial, viral and tumour antigens. Recently, an alternative delivery system based on a genetically modified mutant of the non-pathogenic commensal bacterium Escherichia coli, was developed and successfully used to deliver therapeutic genes and immunogenic proteins to epithelial cells in vivo. In this work, we used these recombinant invasive bacteria to deliver DNA vaccines against two Mycobacterium tuberculosis proteins (FbpA, and HtpX) following intranasal administration. Both DNA vaccines were able to induce an antigen-specific T-cell response. Moreover, mice immunized with the recombinant bacteria carrying the DNA vaccine encoding HtpX, were significatively protected from challenge with M. tuberculosis.     

HIV-infected patients show impaired cellular immune response to influenza vaccination compared to healthy subjects

Detailed data on cellular immune response to influenza vaccination in HIV-infected patients are lacking. We analyzed cellular (IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, IFN-γ, TNF-α, GM-CSF) and humoral (IgG and IgM) immune response in 81 HIV-infected and 30 HIV-negative subjects, before (T0) and 4 weeks (T1) after receiving a single dose of trivalent MF59-adjuvanted influenza vaccine. No difference in humoral response (IgG or IgM) was demonstrated between the two groups. While an increase in most cytokines from T0 to T1 was observed in HIV-uninfected subjects, cytokines production did not significantly increased in HIV-infected patients. Exploring Th1 response, higher CD8 cells count was significantly associated with lower post-vaccination IFNγ levels, while a higher CD4 cells count was associated with a greater response. Exploring Th2 response, higher HIV viral load was significantly associated with reduced post-vaccination IL-10 levels. In conclusion, in HIV-infected patients influenza vaccination could have good efficacy in sustaining humoral response but cellular response appeared impaired.